Pterygium and genetic polymorphism of DNA double strand break repair gene Ku70.

PURPOSE

UV irradiation can produce a wide range of DNA damage, which will lead to gene mutation and uncontrolled cell proliferation. Of the many types of DNA damage, DNA double strand breaks (DSBs) are the most serious form, because of the intrinsic difficulty of their repair, inaccurate repair, or a lack of repair of DSBs can lead to mutations and large-scale genomic instability. DSBs are repaired by the DNA double strand break repair system. The DNA double strand break repair system consists of homologous recombination (HR) and nonhomologous end-joining (NHEJ). In humans, NHEJ is the predominant repair system and Ku70 protein plays an initial and important role in the NHEJ system. Genetic polymorphisms in NHEJ genes influence their DNA repair capacity and confer predisposition to UV-induced skin cancer. Because pterygium is an UV-related uncontrolled cell proliferation, it is logical to assume polymorphisms of Ku70 is associated with genetic predisposition to pterygium.

METHODS

One hundred and twenty eight pterygium patients and 114 volunteers without pterygium were enrolled in this study. Polymerase chain reaction based analysis was used to resolve the Ku70 promoter G-57C (rs2267437) and T-991C (rs5751129) polymorphisms.

RESULTS

There were significant differences between pterygium and control groups in the distribution of genotype (p=0.013) and allelic frequency (p=0.005) in the Ku70 promoter T-991C polymorphism. Individuals who carried at least one C allele (T/C and C/C) had a 2.83 fold increased risk of developing pterygium compared to those who carried the T/T wild type genotype (OR=2.83; 95% CI: 1.38-5.82). Moreover, individuals who carried at least one C allele (T/C and C/C) had a higher tendency to develop both sides of pterygium. In the Ku70 promoter C-57G polymorphism, there was no difference between both groups in the distribution of either genotype or allelic frequency.

CONCLUSIONS

The Ku70 promoter T-991C, but not the Ku70 promoter C-57G polymorphism, is correlated with pterygium. The Ku70 promoter T-991C polymorphism might become a potential marker for the prediction of pterygium susceptibility. It also provides a valuable insight into the pathogenesis of pterygium.